The present invention provides, among other things, methods and compositions for treating complement mediated disease. In some embodiments, recombinant human C1 esterase inhibitor proteins having similar or longer half-life than native plasma-derived human C1 esterase inhibitor, and methods of making the same are provided. In some embodiments, the invention provides a method for administering an effective amount of a recombinant human C1 esterase inhibitor protein to an individual who is suffering from or susceptible to a complement-mediated disease such that at least one symptom or feature of said complement-mediated disease is prevented and/or reduced in intensity, severity, or frequency.
