We review the effect of methylphenidate, focusing on Osmotic-controlled Release Oral delivery System (OROS) methylphenidate, on cardiovascular system, appetite and growth, sleep, tic, epilepsy, psychiatric and rare adverse events. Although OROS methylphenidate has side effects including increased heart rate or blood pressure, decreased appetite, delayed sleep onset, emergence or aggravation of tics, withdrawal or changes in mood, these effects appeared to be minimal in impact or difficult to distinguish from risk to untreated population and tended to be improved by dose adjustment or drug discontinuation. However, in subjects with underlying cardiac problems, uncontrolled epilepsy, previous psychotic episode, clinicians should pay attention and balance the risk and benefit.