Bispecific antibodies (bsAbs) have gained significant attention due to their dual binding activity, which allows simultaneous targeting of two antigens and synergistic effects beyond those achievable with conventional monospecific antibodies. However, the design and construction of bsAbs face practical challenges due to increased structural complexity, including decreased biophysical stability and the formation of antibody-related impurities. This review highlights key considerations and state-of-the-art engineering principles for designing and constructing bsAbs with diverse molecular formats. The mechanisms of action of bsAbs are categorized into in-trans and in-cis, with in-trans acting by creating physical linkages between cells or molecules, and in-cis acting by activating receptors on the same cell. The role of the Fc region in bsAbs is discussed, including its importance in effector functions and engineering strategies to enhance or reduce these functions. Symmetric and asymmetric bsAbs are compared, with symmetric bsAbs having a more straightforward assembly process but limited valency flexibility, while asymmetric bsAbs offer more flexibility in valency and can mimic the native IgG geometry. The importance of proper chain pairing and molecular geometry in achieving the desired therapeutic functionality is emphasized, along with the need for developability considerations such as expression, stability, and aggregation. The review concludes by discussing the promising therapeutic potential of bsAbs and the ongoing efforts to optimize their design and construction.Bispecific antibodies (bsAbs) have gained significant attention due to their dual binding activity, which allows simultaneous targeting of two antigens and synergistic effects beyond those achievable with conventional monospecific antibodies. However, the design and construction of bsAbs face practical challenges due to increased structural complexity, including decreased biophysical stability and the formation of antibody-related impurities. This review highlights key considerations and state-of-the-art engineering principles for designing and constructing bsAbs with diverse molecular formats. The mechanisms of action of bsAbs are categorized into in-trans and in-cis, with in-trans acting by creating physical linkages between cells or molecules, and in-cis acting by activating receptors on the same cell. The role of the Fc region in bsAbs is discussed, including its importance in effector functions and engineering strategies to enhance or reduce these functions. Symmetric and asymmetric bsAbs are compared, with symmetric bsAbs having a more straightforward assembly process but limited valency flexibility, while asymmetric bsAbs offer more flexibility in valency and can mimic the native IgG geometry. The importance of proper chain pairing and molecular geometry in achieving the desired therapeutic functionality is emphasized, along with the need for developability considerations such as expression, stability, and aggregation. The review concludes by discussing the promising therapeutic potential of bsAbs and the ongoing efforts to optimize their design and construction.