Colorectal cancer (CRC) is still one of the most common cancer types in the western world. Women develop the disease later and less often than men but survival does not seem to significantly differ. Estrogens appear to have a protective effect in the development of CRC, although the exact mechanism is not known. Primary tumor location and the molecular characteristics are also different between men and women. Of clinical relevance, right-sided cancers and cancers with high microsatellite instability (MSI-H) are more common in women. Women participate more often in screening programs in general, while the efficacy of screening is higher in men. There are no prospective, gender-specific data from clinical trials regarding the efficacy or toxicity of systemic therapy in the adjuvant or palliative therapeutic setting. Retrospective data from controlled studies have revealed differences in 5‑fluorouracil and irinotecan toxicity. With respect to efficacy, there may be certain gender-specific differences regarding anti-epidermal growth factor receptor (EGFR) antibodies, with women showing somewhat less benefit compared to men.