The unique properties of nucleic acid aptamers and their suitability to therapeutic applications have attracted the attention of researchers for more than 2 decades. Aptamers exhibit significant advantages relative to antibody-based therapeutics and can serve dual roles as either the therapeutic agent itself or a targeting modality. Despite this intense research interest, aptamers have been slow to reach the clinic, partly due to practical limitations that can be overcome by rational chemical modifications and ingenious aptamer selection approaches. This review highlights the latest efforts to use aptamers in therapeutic applications, the key properties of aptamers that can be exploited, the aptamers that are currently in clinical trials, as well as speculation on the future of aptamers in the field of nanomedicine.