Hematopoietic cell transplantation (HCT) is an essential component of potentially curative therapy for patients with hematologic malignancies. High‐dose chemotherapy with autologous (auto) stem cell rescue is used to overcome chemoresistance in multiple myeloma, non‐Hodgkin lymphoma, and Hodgkin lymphoma. Alternatively, poor‐risk acute leukemias rely on the graft versus leukemia effect of allogeneic (allo) products. Long‐term remissions are feasible with both auto‐ and allo‐HCT; however, disease relapse is the leading cause of death after HCT for many patients. In recognition of this, novel therapies are being investigated in the upfront, relapsed/refractory, and post‐HCT maintenance settings to deepen response and maintain disease control. To date, the most robust data to support this approach are in multiple myeloma, where post‐transplant maintenance therapy has improved clinical outcomes. In Hodgkin lymphoma, patients with high‐risk features may benefit from post–auto‐HCT vedotin (BV) regardless of pre‐HCT BV exposure. Apart from mantle cell lymphoma, where rituximab maintenance is generally accepted, post–auto‐HCT maintenance in other forms of NHL is less established. In patients who undergo allo‐HCT, the utilization of maintenance therapy is an important component of improving post‐HCT outcomes, however, an individualized approach that considers patient factors such as residual toxicity from HCT, an immature graft with poor graft function, infection, and graft‐versus‐host disease create a complex environment for aggressive interventions. Initiation of directed agents in patients with identified mutations prior to allo‐HCT, including FLT3 in acute myeloid leukemia and Philadelphia chromosome in acute lymphoid leukemia have generally improved post‐HCT outcomes. Ongoing studies are exploring the safety and efficacy of additional maintenance strategies post–allo‐HCT in an effort to further improve post‐HCT outcomes.