The recent approvals of four CD19‐or CD22‐targeted therapies for B‐cell acute lymphoblastic leukemia (B‐ALL) have transformed the treatment of relapsed/refractory (r/r) disease. Adults with r/r B‐ALL are usually eligible for all options, but there are no studies directly comparing these agents, and the treating physician must decide which to select. Each therapy has notable activity as a single agent but has limitations in particular settings, and the optimal choice varies. These therapies can be complementary and used either sequentially or concomitantly. Here, we review the current landscape of antigen‐targeted therapies for r/r B‐ALL and discuss considerations for their use.