Randomness has multiple uses in science, art, statistics, cryptography, gaming, gambling, and other fields. For example, random assignment in randomized controlled trials helps scientists to test hypotheses, and random numbers or pseudorandom numbers help video games such as video poker.

These uses have different levels of requirements, which leads to the use of different methods. Mathematically, there are distinctions between randomization, pseudorandomization, and quasirandomization, as well as between random number generators and pseudorandom number generators. For example, applications in cryptography usually have strict requirements, whereas other uses (such as generating a "quote of the day") can use a looser standard of pseudorandomness.

Unpredictable (by the humans involved) numbers (usually taken to be random numbers) were first investigated in the context of gambling developing, sometimes, pathological forms like apophenia. Multiple randomizing devices such as dice, shuffling playing cards, and roulette wheels, seem to have been developed for use in games of chance. Electronic gambling equipment cannot use these and so theoretical problems are less easy to avoid; methods of creating them are sometimes regulated by governmental gaming commissions.

Modern electronic casino games contain often one or more random number generators which decide the outcome of a trial in the game. Even in modern slot machines, where mechanical reels seem to spin on the screen, the reels are actually spinning for entertainment value only. They eventually stop exactly where the machine's software decided they would stop when the handle was first pulled. It has been alleged that some gaming machines' software is deliberately biased to prevent true randomness, in the interests of maximizing their owners' revenue; the history of biased machines in the gambling industry is the reason government inspectors attempt to supervise the machines—electronic equipment has extended the range of supervision. Some thefts from casinos have used clever modifications of internal software to bias the outcomes of the machines—at least in those which have been discovered. Gambling establishments keep close track of machine payouts in an attempt to detect such alterations.

Random draws are often used to make a decision where no rational or fair basis exists for making a deterministic decision, or to make unpredictable moves.

Fifth century BC Athenian democracy developed out of a notion of isonomia (equality of political rights), and random selection was a principal way of achieving this fairness. Greek democracy (literally meaning "rule by the people") was actually run by the people: administration was in the hands of committees allotted from the people and regularly changed. Although it may seem strange to those used to modern liberal democracy, the Athenian Greeks considered elections to be essentially undemocratic. This was because citizens chosen on merit or popularity contradicted the democratic equality of all citizenry. In addition, allotment prevented the corrupt practice of buying votes as no one could know who would be selected as a magistrate, or to sit on a jury.

Allotment, also called sortition, is today used in the selection of jurors in Anglo-Saxon legal systems like the UK and United States. Proposals have been made for its use in government such as a new constitution for Iraq and various proposals for Upper Houses chosen by allotment—see Reform of the House of Lords § Allotment (sortition). Scholars have studied the potential of random selection of personnel in politics and organizations.

Random numbers have uses in physics such as electronic noise studies, engineering, and operations research. Multiple methods of statistical analysis, such as the bootstrap method, require random numbers. Monte Carlo methods in physics and computer science require random numbers.