Intradialytic hypotension (IDH) is the most frequent complication of hemodialysis (HD) treatments with a frequency of 10% to 12% for patients with chronic kidney disease attending for outpatient treatments and is associated with both temporary ischemic stress to vital organs, including the heart and brain, and increased patient mortality. Although there have been many different definitions of IDH over the years, an absolute nadir systolic blood pressure (SBP) has the strongest association with patient outcomes. The unifying pathophysiology is one of reduced effective blood volume, resulting in lower plasma tonicity, and if this cannot be adequately compensated for by activation of neurohumeral systems, then arteriolar tone and blood pressure fall. The risk factors for developing IDH are numerous, ranging from patient-related factors, including age and comorbidity with reduced cardiac reserve, to patient compliance with dietary and lifestyle advice, to reactions with the extracorporeal circuit and medications, choice of dialysate composition and temperature, setting of postdialysis target weight, ultrafiltration rate, and profiling. Advances in dialysis machine technology by providing real time estimates of the effective circulating volume and adjusting dialysate composition to maintain vascular tonicity are being developed, but currently require more sophisticated biofeedback loops to be clinically effective in preventing IDH. While awaiting advances in artificial intelligence, the clinician continues to rely on patient education to limit interdialytic weight gains, frequent assessment of the postdialysis target weight, adjusting dialysate composition and temperature, introducing convective therapies to increase thermal losses, and altering dialysis session duration and frequency to reduce ultrafiltration rate requirements.