Parenteral nutrition (PN) has been successfully initiated in the home since the early 1990s. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Standards for Specialized Nutrition Support: Home Care Patients, Safe Practices for Parenteral Nutrition, and Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients do not contain specific information on the initiation of home PN (HPN). Peer-reviewed, published guidelines are necessary to provide safe and appropriate initiation of HPN. Certain patients should not have PN initiated in the home, such as those with organ failure, uncontrolled diabetes, or uncorrectable electrolyte abnormalities. Excellent candidates for initiation of HPN include patients who have failed enteral feedings, have gastrointestinal (GI) diseases without excessive GI losses, or those with an oncology diagnosis and inability to tube feed. One concern of initiation of HPN is the potential for refeeding syndrome. Refeeding syndrome can be prevented when patients are properly evaluated and managed before initiation of PN. Refeeding syndrome can be avoided by rehydration with fluid and electrolytes before initiation of HPN to normalize blood chemistry when necessary and by starting with a moderate-volume, low-carbohydrate HPN solution compounded with optimal potassium, phosphorus, and magnesium content, and slowly advanced to goal. The “start low and go slow” motto of nutrition support should continue to be followed, but more specific guidelines are needed to assist nutrition support clinicians with safe and appropriate initiation of HPN.