The invention relates to albumin fusion proteins comprising an albumin fusion partner and a protease inhibitor fusion partner which may be a Kunitz domain protease inhibitor capable of inhibiting a serine protease, including neutrophil elastase, kallikrein, and plasm The fusion proteins exhibit extended shelf life and/or extended therapeutic activity in solution. The invention encompasses therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits comprising the albumin fusion proteins, a well as nucleic acid molecules encoding the albumin fusion proteins, vectors comprising these nucleic acids, host cells transformed w these nucleic acids and vectors, and methods of making the encoded proteins using the nucleic acids, vectors and/or host cells. The invention also relates to compositions and methods for inhibiting neutrophil elastase, kallikrein, and plasmin, and to compositions an methods for treating cystic fibrosis and cancer.