There is an unquestionable need for more effective therapies for pancreatic cancer. Aptamers are single-stranded DNA or RNA oligonucleotide ligands whose 3-dimensional structures are dictated by their sequences. Aptamers have been generated against numerous purified protein targets using an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Several biochemical properties make them attractive tools for use in an array of biological research applications and as potential pharmacologic agents. Isolated aptamers may directly affect target protein function, or they may also be modified for use as delivery agents for other therapeutic cargo or as imaging agents. More complex selections, using whole cancer cells or tumor tissue, may simultaneously identify novel or unexpected targets and aptamers to inhibit them. This review summarizes recent advances in the field of aptamers and discusses aptamer targets that have relevance to pancreatic cancer.