Aptamers are emerging as promising therapeutic agents for cancer treatment. This chapter covers the complete journey of aptamer therapy from basic concepts to clinical use. The chapter begins with aptamer technology’s history, focusing on how the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method evolved to select highly specific molecular recognition elements. It then explains why aptamers are valuable for cancer therapy, highlighting their advantages, like small size, low immunogenicity, and excellent target specificity. The text discusses how researchers optimize aptamers through chemical modifications to improve stability and develop new drug conjugation methods. It reviews US Food and Drug Administration (FDA)-approved aptamer drugs and ongoing clinical trials. Recent innovations covered include intelligent delivery systems, switchable aptamers, and theranostic applications that combine diagnosis with treatment. The chapter provides a balanced view by addressing current limitations and potential solutions. By connecting fundamental aptamer science with clinical applications, this chapter helps advance aptamer-based cancer treatments.