Monoclonal antibodies (mAbs) are widely used in treating various diseases, including cancer, autoimmune disorders, and infectious diseases. However, their administration can lead to serious adverse effects such as acute anaphylaxis, serum sickness, and cytokine release syndrome (CRS). These events are often related to the specific targets of the mAbs or their mechanisms of action. For example, TGN1412, a CD28-specific mAb, caused a life-threatening cytokine release syndrome in a first-in-human trial, leading to recommendations for improved safety in clinical studies. mAbs are generally well-tolerated, but they can cause immune reactions, including hypersensitivity and infusion reactions. These reactions can range from mild skin reactions to severe systemic inflammatory responses. The development of fully human mAbs has reduced immunogenicity, but some mAbs, such as rituximab and natalizumab, can still cause severe adverse effects, including progressive multifocal leukoencephalopathy (PML) and thrombocytopenia. Infections are a significant side effect of mAbs, particularly those targeting TNFα, which can increase the risk of tuberculosis and lymphomas. Additionally, some mAbs can cause autoimmune diseases, such as lupus-like syndromes and thyroid autoimmunity. Cardiotoxicity is another major concern, with trastuzumab causing cardiac dysfunction in some patients. The development of mAbs has also raised concerns about their potential to cause tumour progression. Some mAbs, such as infliximab, have been associated with an increased risk of malignancies. However, the relationship between mAb therapy and cancer is complex and requires further research. To minimize these risks, preclinical testing and antibody technology have been developed. These include strategies to reduce immunogenicity, such as using IgG4 isotypes and modifying the Fc region. Additionally, regulatory guidelines have been established to improve the safety of mAb therapies, including the use of microdosing studies and in vitro tests to predict the risk of CRS. Overall, while mAbs have revolutionized the treatment of many diseases, their use requires careful consideration of potential adverse effects and the development of strategies to minimize these risks.Monoclonal antibodies (mAbs) are widely used in treating various diseases, including cancer, autoimmune disorders, and infectious diseases. However, their administration can lead to serious adverse effects such as acute anaphylaxis, serum sickness, and cytokine release syndrome (CRS). These events are often related to the specific targets of the mAbs or their mechanisms of action. For example, TGN1412, a CD28-specific mAb, caused a life-threatening cytokine release syndrome in a first-in-human trial, leading to recommendations for improved safety in clinical studies. mAbs are generally well-tolerated, but they can cause immune reactions, including hypersensitivity and infusion reactions. These reactions can range from mild skin reactions to severe systemic inflammatory responses. The development of fully human mAbs has reduced immunogenicity, but some mAbs, such as rituximab and natalizumab, can still cause severe adverse effects, including progressive multifocal leukoencephalopathy (PML) and thrombocytopenia. Infections are a significant side effect of mAbs, particularly those targeting TNFα, which can increase the risk of tuberculosis and lymphomas. Additionally, some mAbs can cause autoimmune diseases, such as lupus-like syndromes and thyroid autoimmunity. Cardiotoxicity is another major concern, with trastuzumab causing cardiac dysfunction in some patients. The development of mAbs has also raised concerns about their potential to cause tumour progression. Some mAbs, such as infliximab, have been associated with an increased risk of malignancies. However, the relationship between mAb therapy and cancer is complex and requires further research. To minimize these risks, preclinical testing and antibody technology have been developed. These include strategies to reduce immunogenicity, such as using IgG4 isotypes and modifying the Fc region. Additionally, regulatory guidelines have been established to improve the safety of mAb therapies, including the use of microdosing studies and in vitro tests to predict the risk of CRS. Overall, while mAbs have revolutionized the treatment of many diseases, their use requires careful consideration of potential adverse effects and the development of strategies to minimize these risks.