From ancient times to today, drug discovery transitioned from serendipity to rationality over its long history. Proper drug target selection and validation are crucial to the discovery of new drugs. This review discusses the definition of drug targets and proposes several characteristics for drug targets. The limitations of the term 'target' itself are summarized. The drug target validation process is also discussed in detail and pitfalls during this process are outlined. Small active chemical compounds obtained from the target validation process are useful tools in target validation and target function research. The validation of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) as a new potential anti-atherosclerotic drug target is cited as an example in order to elucidate the target validation process.