Clinicians caring for patients on peritoneal dialysis (PD) have relied on a variety of laboratory measures to assess the health of patients and their response to treatment. Traditionally, serum albumin has been an indicator of nutrition status and has therefore been included in monthly blood testing in most centers. The development of hypoalbuminemia in dialysis patients has been associated with increased mortality and often leads to interventions such as trials of nutritional supplements. In PD, hypoalbuminemia combined with ongoing losses of protein into effluent raise particular concerns with clinicians. Serum albumin may be affected by a variety of non-nutrition factors such as inflammation, volume status, and comorbidities. Albumin synthesis in the liver exceeds, in most cases, albumin losses in urine or effluent. Interpreting the medical implications of declining serum albumin in PD patients can therefore be a challenge. This paper reviews protein balance in PD. The nutritional and non-nutritional factors affecting serum albumin are discussed, with specific emphasis on how membrane physiology contributes to dialysate protein losses. A general clinical approach to the PD patient developing hypoalbuminemia is discussed.