Systematic evolution of ligand by exponential enrichment (SELEX) is an efficient method used to isolate high-affinity single stranded oligonucleotides from a large random sequence pool. These SELEX-derived oligonucleotides named aptamer, can be selected against a broad spectrum of target molecules including proteins, cells, microorganisms and chemical compounds. Like antibodies, aptamers have a great potential in interacting with and binding to their targets through structural recognition and are therefore called "chemical antibodies". However, aptamers offer advantages over antibodies including smaller size, better tissue penetration, higher thermal stability, lower immunogenicity, easier production, lower cost of synthesis and facilitated conjugation or modification with different functional moieties. Thus, aptamers represent an attractive substitution for protein antibodies in the fields of biomarker discovery, diagnosis, imaging and targeted therapy. Enormous interest in aptamer technology triggered the development of SELEX that has underwent numerous modifications since its introduction in 1990. This review will discuss the recent advances in SELEX methods and their advantages and limitations. Aptamer applications are also briefly outlined in this review.