Combined oral contraceptives (COCs), oral contraceptives containing an estrogen and a progestin, are a common, effective, and generally well-tolerated form of contraception with a wide variety of noncontraceptive benefits. Combined oral contraceptives have been most limited by the potential severe adverse event of venous thromboembolism throughout their history and development. In recent years, natural-estrogen-containing COCs have emerged with an improved safety profile while maintaining high efficacy and should likely be recommended as first line for new-start patients. It is important for clinicians to understand the evolution of COC regimens and the specific hormones within each formulation to best optimize benefits while minimizing risks to patients.