Cancer treatments can be detrimental to fertility; recent literature has focused on the efforts of fertility preservation for this patient population. It should be recognized, however, that several nonmalignant medical conditions and therapeutic interventions could be similarly hazardous to fertility. Some of these nonmalignant diseases and their treatments that can adversely impact the reproductive axis are gastrointestinal diseases, rheumatologic disorders, nonmalignant hematologic conditions, neurologic disorders, renal disorders, gynecologic conditions, and metabolic diseases. Their negative effects on reproductive function are only now being appreciated and include impaired ovarian function, endocrine function, or sexual function and inability to carry a pregnancy to term. Complications and comorbidities associated with certain diseases may limit the success of established fertility preservation options. Recent advances in fertility preservation techniques may provide these patients with new options for childbearing. Here, we review several fertility-threatening conditions and treatments, describe current established and experimental fertility preservation options, and present three initiatives that may help minimize the adverse reproductive effects of these medical conditions and treatments by raising awareness of the issues and options: (1) increase awareness among practitioners about the reproductive consequences of specific diseases and treatments, (2) facilitate referral of patients to fertility-sparing or restorative programs, and (3) provide patient education about the risk of infertility at the time of diagnosis before initiation of treatment.