With improved treatment strategies and prognosis for patients with Hodgkin lymphoma (HL), interest has increasingly focused on high-risk groups. These groups include a small proportion of patients who experience relapse or who have primary refractory disease despite state-of-the-art treatment. Although many research efforts have been made in this field, specific biological markers that reliably predict unfavorable outcome during first-line treatment are lacking. Recent analyses in HL and other malignancies, however, have demonstrated an important impact of patient-related factors, such as individual differences in hematologic toxicity and drug metabolism, on disease outcome. A different cytochrome enzyme status and slower drug clearance in female patients, resulting in higher systemic toxicity and effectiveness of treatment, indicate that sex-specific aspects are important. In this Review, we discuss the current data on hematotoxicity among male and female patients with HL and other malignancies. In addition, we highlight the potential causes of hematotoxicity and its impact on treatment outcome and the role of future strategies.