Bispecific antibodies (BsAbs) are a promising class of targeted therapies for B-cell non-Hodgkin lymphoma (B-NHL), particularly in relapsed/refractory (R/R) settings where conventional treatments have limited efficacy. BsAbs, such as mosunetuzumab and glofitamab, target CD20 on B-cells and CD3 on T-cells, enabling T-cell activation and tumor cell killing. These therapies have shown significant clinical activity, with high overall response rates (ORR) and complete response (CR) rates in R/R FL and DLBCL. Mosunetuzumab, a CD20xCD3 BsAb, demonstrated an ORR of 80% and CR rate of 60% in R/R FL, with durable responses and manageable safety profiles. Glofitamab also showed promising results in R/R DLBCL and MCL, with high ORR and CR rates. Epcoritamab, another CD20xCD3 BsAb, achieved high ORR and CR rates in R/R FL and DLBCL, with favorable safety profiles. BsAbs offer advantages over traditional therapies, including reduced toxicity and the potential for off-the-shelf availability. However, challenges such as cytokine release syndrome (CRS) and T-cell exhaustion remain. Strategies to mitigate these risks include step-up dosing, pre-treatment with anti-CD20 monoclonal antibodies, and combination therapies with other agents like lenalidomide or PV. Combination therapies with BsAbs and other effective agents, such as lenalidomide or PV, are being explored to enhance efficacy and reduce toxicity. Future perspectives include the development of trispecific antibodies (TsAbs) and combinations with NK cells, which may improve T-cell activation and overcome immune escape. Additionally, the optimal administration settings, pre-treatment strategies, and treatment duration for BsAbs need further investigation. Identifying biomarkers of response and resistance mechanisms is crucial for personalized treatment approaches. BsAbs represent a promising advancement in the treatment of B-NHL, offering a new therapeutic option with potential for improved outcomes in R/R settings.Bispecific antibodies (BsAbs) are a promising class of targeted therapies for B-cell non-Hodgkin lymphoma (B-NHL), particularly in relapsed/refractory (R/R) settings where conventional treatments have limited efficacy. BsAbs, such as mosunetuzumab and glofitamab, target CD20 on B-cells and CD3 on T-cells, enabling T-cell activation and tumor cell killing. These therapies have shown significant clinical activity, with high overall response rates (ORR) and complete response (CR) rates in R/R FL and DLBCL. Mosunetuzumab, a CD20xCD3 BsAb, demonstrated an ORR of 80% and CR rate of 60% in R/R FL, with durable responses and manageable safety profiles. Glofitamab also showed promising results in R/R DLBCL and MCL, with high ORR and CR rates. Epcoritamab, another CD20xCD3 BsAb, achieved high ORR and CR rates in R/R FL and DLBCL, with favorable safety profiles. BsAbs offer advantages over traditional therapies, including reduced toxicity and the potential for off-the-shelf availability. However, challenges such as cytokine release syndrome (CRS) and T-cell exhaustion remain. Strategies to mitigate these risks include step-up dosing, pre-treatment with anti-CD20 monoclonal antibodies, and combination therapies with other agents like lenalidomide or PV. Combination therapies with BsAbs and other effective agents, such as lenalidomide or PV, are being explored to enhance efficacy and reduce toxicity. Future perspectives include the development of trispecific antibodies (TsAbs) and combinations with NK cells, which may improve T-cell activation and overcome immune escape. Additionally, the optimal administration settings, pre-treatment strategies, and treatment duration for BsAbs need further investigation. Identifying biomarkers of response and resistance mechanisms is crucial for personalized treatment approaches. BsAbs represent a promising advancement in the treatment of B-NHL, offering a new therapeutic option with potential for improved outcomes in R/R settings.