Objectives: Psychiatric disorders are common in patients on hemodialysis. To the best of our knowledge there are no reported cases of psychosis developing in hemodialysis patients in the context of nephrectomy, and there is limited data on the use of long-acting antipsychotics in hemodialysis, which are generally not recommended in chronic kidney disease. Methods: We present the case of a 40-year-old lady with bilateral nephrectomy receiving hemodialysis who developed psychosis that resulted in her refusing to continue hemodialysis and was irregularly compliant with oral antipsychotics, necessitating the use of a long-acting injection. We report on the approach to clinical reasoning in the choice of aripiprazole and the need for a long-acting injection. Results: Based on its pharmacological and pharmacokinetic properties oral aripiprazole 20mg was commenced and after establishing tolerability and response, the patient was switched to long-acting aripiprazole 400mg monthly achieving full remission of psychotic symptoms after 6 months with maintained improvement after 12 months. Conclusion: Based on its properties, aripiprazole may be a reasonable option in the treatment of psychosis in patients on hemodialysis with nephrectomy and can be considered even as a long-acting injection in these patients.