Monoclonal antibodies (MAbs), guided by molecular studies and personalised medicine are changing the face of clinical medicine. They hold the promise of controlling diseases and improving survival whilst reducing the side effects of some ‘traditional’ therapies. MAbs are being used in conditions familiar to intensivists such as asthma, invasive candidiasis, RSV infection, reversal of novel anticoagulants and clostridium difficile infection as well as in those less commonly seen by intensivists such as multiple sclerosis, migraine, rheumatoid arthritis and numerous malignancies. Side effects of MAb treatment pose particular challenges for intensivists and range from cytokine release syndrome to autoimmune states (such as colitis, endocrinopathies, skin reactions), pneumonitis, thromboemboli, and infections. Pharmcokinetic interactions of MAbs with other drugs remain poorly studied and may be immune dependent, cytokine dependent or target dependent. Our traditional approach of triaging patients for ICU, based on organ failures and ‘prognosis of underlying disease’ is going to be challenged by MAbs with their disease modifying properties and unique side effects.