In patients with acute lymphoblastic leukemia (ALL), although 80-90% of adult patients achieve a complete response (CR), cure rates are only 40% with initial treatment and 10%-20% with subsequent salvage treatments. Ten percent of patients are refractory to initial treatment, and 40%-70% relapse. Allo-HCT is the standard of care for a fit and eligible group. Immunotherapies are an important choice in improving treatment success and reducing side effects. The primary immunotherapies include bispecific antibodies (BsAbs), antibody-drug conjugates, CAR T-cell, and CAR NK-cell therapies. Blinatumomab activates T cells by binding to CD19 on B-ALL cells and CD3 on T cells, leading to polyclonal expansion of cytotoxic T cells, T-cell activation, and the release of cytokines and cytotoxic granules. thus causing lysis of CD19+ lymphoblasts. It is approved for the treatment of Ph(-) Relapsed/Refractory (R/R) B-ALL and has received FDA approval for consolidation therapy in patients with MRD-positive disease and for MRD-independent consolidation therapy. The Alcantara study demonstrated sustained responses in patients with Ph(+) R/R ALL. Inotuzumab is an antibody-drug conjugate containing calicheamicin, an anti-CD22-targeted, DNA-binding cytotoxic antibiotic. It received FDA approval after inotuzumab monotherapy demonstrated superiority over standard chemotherapy for relapsed/refractory CD22(+) B-ALL. The most common Grade ≥3 adverse events were hematologic and liver-related and included an 11% VOD, mostly seen after sequential allo-HSCT. Inotuzumab monotherapy has shown high CR and MRD negativity rates when used in combination with reduced-intensity chemotherapy in the first-line setting in elderly patients. Cell-based therapies have demonstrated efficacy in R/RB-ALL with CD19-targeted therapies such as tisagen-lecleucel (tisa-cel) for patients aged ≤25 years and brexucabtagene autoleucel for adults, despite the side effects that limit CAR T cells. Side effects include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), and B-cell aplasia. Studies of CD5-CART, CD7-CART, and NS7CAR are ongoing for relapsed/refractory T-cell leukemia. Although experimental, CAR-NK therapies, which use NK cells isolated from peripheral blood and do not pose a risk of GVHD, show promise with fewer side effects, fewer relapses, and longer survival. Studies of immune checkpoint inhibitors combined with other immunotherapies may be important for B-ALL, while combinations of BCL-2 and BCL-XL inhibitors with chemotherapy may be important for T-ALL, for which no antibody therapy is currently available. Difficulties continue to arise in the treatment of T-ALL and Ph-like ALL. Immunotherapy and cellular therapies are being studied in optimal combinations.