Cytokine release syndrome (CRS) is a common acute toxicity in T-cell therapies, including T-cell engaging bispecific antibodies (T-BiSp). Effective CRS management and prevention is crucial in T-BiSp development. Required hospitalization for 7 of the 9 approved T-BiSp and the need for clinical intervention in severe cases highlight the importance of mitigation strategies to reduce healthcare burden and improve patient outcome. In this review, we discuss the emerging evidence on CRS mitigation, management, and prediction. We cover different strategies for dose optimization, current and emerging (pre)treatment strategies, quantitative pharmacology tools employed during drug development, and biomarkers and predictive factors. Insights are gleaned on step-up dosing and formulation effects on CRS and CRS relationships with cytokine dynamics and drug levels gathered through review of T-BiSp licensing applications and emerging data from conferences and publications.