Patients on peritoneal dialysis (PD) suffer from a high incidence of cardiovascular disease as compared to healthy individuals, and a markedly increased mortality that cannot fully be explained by traditional risk factors. Recent evidence suggests that end-stage renal disease is a state of systemic inflammation and oxidative stress, both of which appear to play an important role in the development of cardiovascular disease. Here, we review recent data looking at the impact of persistent inflammation (usually recognized by elevated serum levels of C-reactive protein) on morbidity and mortality in PD-patients. While many causes of inflammation are attenuated with PD, including volume overload and biocompatibility of membranes, PD is also associated with modality-specific causes of inflammation such as peritonitis, glucose degradation products and fluid bioincompatibility. Additionally, PD can lead to the uptake of large amounts of glucose from the fluid, resulting in a risk of increased oxidative stress, which also may contribute to inflammation. In addition, recent research shows that genetic factors are clinically important in determining inflammatory response. Finally, we briefly explore potential strategies specifically aiming at reducing intraperitoneal and systemic inflammation in PD patients.