Malabsorption of nutrients in cystic fibrosis (CF) has a multifactorial origin. The factors involved in malabsorption include malfunction of the exocrine pancreas and liver, bile acid metabolism, and disordered intestinal resorptive processes. Therapeutic measures presently employed are only partially effective. Improvement of fat malabsorption is attained by using a pancreatic enzyme supplement consisting of pH-sensitive, enteric-coated microspheres (microsphere preparations) that prevent enzyme degradation in the stomach and travel with the chyme to the small intestine. Microsphere preparations, however, do not improve bile salt deficiency. The detergent Tween-80, given orally to simulate bile salt activity, does not improve fat absorption. The mucus viscosity is probably enhanced in the intestinal epithelium of CF patients and can be decreased by N-acetylcysteine, which breaks down sulfide bonds. However, the addition of a high oral dose of this mucus solvent to pancreatin preparations does not improve fat absorption. Further studies on the disturbed intestinal resorptive mechanism seem warranted since recent investigations point to an abnormal chloride secretion as the primary defect in the intestinal epithelia of CF patients.