Flash drives implement the USB mass storage device class so that most modern operating systems can read and write to them without installing device drivers. The flash drives present a simple block-structured logical unit to the host operating system, hiding the individual complex implementation details of the various underlying flash memory devices. The operating system can use any file system or block addressing scheme. Some computers can boot up from flash drives.

Installers of some operating systems can be stored to a flash drive instead of a CD or DVD, including various Linux distributions, Windows 7 and newer versions, and macOS. In particular, Mac OS X 10.7 is distributed only online, through the Mac App Store, or on flash drives; for a MacBook Air with Boot Camp and no external optical drive, a flash drive can be used to run installation of Windows or Linux.
Some manufacturers, aiming at a "best of both worlds" solution, have produced card readers that approach the size and form of USB flash drives (e.g., Kingston MobileLite,[65] SanDisk MobileMate[66]) These readers are limited to a specific subset of memory card formats (such as SD, microSD, or Memory Stick), and often completely enclose the card, offering durability and portability approaching, if not quite equal to, that of a flash drive. Although the combined cost of a mini-reader and a memory card is usually slightly higher than a USB flash drive of comparable capacity, the reader + card solution offers additional flexibility of use, and virtually "unlimited" capacity. The ubiquity of SD cards is such that, circa 2011, due to economies of scale, their price is now less than an equivalent-capacity USB flash drive, even with the added cost of a USB SD card reader.

USB flash drives are portable and easy-to-use data storage devices. They're compatible with desktop computers and laptop computers as well as a broad range of game consoles and media devices. Use them to transfer data between systems, share files with friends and colleagues or create backups of critical information. Staples offers a complete selection of high-capacity thumb drives, including popular brands such as Lexar, PNY, Samsung, SanDisk and Verbatim.

Flash memory cards, e.g., Secure Digital cards, are available in various formats and capacities, and are used by many consumer devices. However, while virtually all PCs have USB ports, allowing the use of USB flash drives, memory card readers are not commonly supplied as standard equipment (particularly with desktop computers). Although inexpensive card readers are available that read many common formats, this results in two pieces of portable equipment (card plus reader) rather than one.

Floppy disk hardware emulators exist which effectively utilize the internal connections and physical attributes of a floppy disk drive to utilize a device where a USB flash drive emulates the storage space of a floppy disk in a solid state form, and can be divided into a number of individual virtual floppy disk images using individual data channels.

In addition to providing reliable storage for information, many of these products come with security software that protects your personal data if you lose your device. The software secures files with 128-bit AES encryption and requires a password to unlock the stored information. It also features a drag-and-drop user interface that simplifies transferring and securing your data.

When used in the same manner as external rotating drives (hard drives, optical drives, or floppy drives), i.e. in ignorance of their technology, USB drives' failure is more likely to be sudden: while rotating drives can fail instantaneously, they more frequently give some indication (noises, slowness) that they are about to fail, often with enough advance warning that data can be removed before total failure. USB drives give little or no advance warning of failure. Furthermore, when internal wear-leveling is applied to prolong life of the flash drive, once failure of even part of the memory occurs it can be difficult or impossible to use the remainder of the drive, which differs from magnetic media, where bad sectors can be marked permanently not to be used.[74]
With wide deployment(s) of flash drives being used in various environments (secured or otherwise), the issue of data and information security remains important. The use of biometrics and encryption is becoming the norm with the need for increased security for data; on-the-fly encryption systems are particularly useful in this regard, as they can transparently encrypt large amounts of data. In some cases a secure USB drive may use a hardware-based encryption mechanism that uses a hardware module instead of software for strongly encrypting data. IEEE 1667 is an attempt to create a generic authentication platform for USB drives. It is supported in Windows 7 and Windows Vista (Service Pack 2 with a hotfix).[47]
As highly portable media, USB flash drives are easily lost or stolen. All USB flash drives can have their contents encrypted using third-party disk encryption software, which can often be run directly from the USB drive without installation (for example, FreeOTFE), although some, such as BitLocker, require the user to have administrative rights on every computer it is run on.
There's a lot to choose from when it comes to buying a flash drive. The most important thing to consider is size. The whole point of a USB drive is to store lots of data in a small space, so think about what kinds of files you'll want to house on your flash drive. Movies and music take quite a bit of space, so if you're carrying your whole entertainment library with you, you'll want a big thumb drive – at least 16GB. Books and other text-based documents require relatively little storage space, so people like students and working professionals using Microsoft Office would be happy transferring Word documents or Excel files with as little as 1GB of space. On the other hand, if you are using photo or music editing software, you'll want a USB flash drive with lots of storage capacity to transfer graphic and music files.