The uremic milieu is consequential to a disrupted balance between availability of retention solutes and the excretory capacity of the kidneys. Although metabolism is the prime contributor to the internal milieu, a significant fraction of uremic retention solutes originates from other sources. The main route of entrance is via the intestinal tract, directly from the diet and indirectly from commensal microbial metabolism. This latter dynamic interplay between the intestines and kidney has been coined the gut-kidney axis. This review summarizes current understanding of the gut-kidney axis and explores the impact of dietary and other nonextracorporeal therapeutic interventions in patients with chronic kidney disease.