Diffuse large B-cell lymphoma, the most common subtype of non-Hodgkin lymphoma, comprises a heterogenous group of morphologically, genetically, and clinically distinct diseases. Several recent advances have affected the treatment landscape, which had been mostly stagnant for the past few decades. We will review the practice-changing studies in frontline (POLARIX), early relapse (ZUMA-7 and TRANSFORM), and multiple recurrent (ZUMA-1, JULIET, TRANSCEND, L-MIND, and LOTIS-2) stages and discuss how the treatment landscape may evolve with the emergence of bispecific antibodies.