End-stage renal disease (ESRD) patients depend on dialysis for removal of toxic waste products, fluid overload relief and maintenance of electrolyte balance. Dialysis prolongs millions of lives. To some extent, ESRD has become a manageable disease with a steadily growing dialysis population of increasing average age and associated comorbidity. During 7 decades many technical refinements have been developed e.g. sodium profiling, blood volume, ultrafiltration variation based on blood pressure measurement, urea kinetics etc. Despite its large potentials, in-line electrolyte monitoring lags behind in dialysis treatment. Areas covered: In this paper, we review the state of technologies available for in-line monitoring of the electrolytes sodium, potassium and calcium during hemodialysis. Expert commentary: We concluded that individual optimization of dialysate composition should be able to improve hard medical outcomes, but practical clinical implementation stands/falls with reliable and affordable in-line ion-selective sensing technology. Optical ion-selective microsensors and microsystems form a promising pathway for individualizing the dialysis treatment.