The global incidence of colorectal adenocarcinoma is stable or decreasing overall; however, the incidence of colorectal cancer in patients aged <50 years is increasing. Although some of this increase is due to hereditary cancer syndromes, this is not the sole explanation. Patients with early-onset rectal cancer in particular have unique disease patterns and face distinct challenges in their treatment. Molecular patterns of disease in this patient cohort are noteworthy and often represent an opportunity to target these cancers more effectively. Recent and ongoing trials focusing on minimizing toxicities and necessary therapy modalities and maximizing response and patient outcome are of paramount importance in this patient population. Additional resources are needed for this patient population, including fertility counseling and preservation, financial guidance, genetic counseling, and psychosocial support.