A 74-year-old female with diabetes mellitus type II and Alzheimer's disease, taking donepezil for 4 months was operated for right modified radical mastectomy under general anesthesia. During the procedure a higher dose of non-depolarizing muscle relaxant was required than those recommended for her age yet the muscle relaxation was inadequate intra-operatively. Residual neuromuscular blockade persisted postoperatively, due to the cumulative effect of large doses of non-depolarizing muscle relaxant, needing post-operative ventilatory assistance. After ruling out other causes of resistance to non-depolarizing muscle relaxants, we concluded that acetylcholinesterase inhibitor donepezil was primarily responsible for inadequate muscle relaxation and delayed post-operative neuromuscular recovery.