Unlike sub-optimal prescribing, rational prescribing, coupled with certain indicators, is associated with improved safety in drug use in terms of selecting appropriate drug for prescribing, better quality of life for patients and cost-effective care. Medication prescribing is a relatively unexplored area of research in Saudi Arabia and until now most studies have been in the secondary and tertiary health care system. This paper is the second of 3 review articles that form the background for a series of 5 interconnected studies of prescribing patterns and medication errors in the public and private primary health care sectors of Saudi Arabia. A MEDLINE search was conducted to identify papers published in peer-reviewed journals over the previous 3 decades. The paper reviews rational prescribing with its indicators, suboptimal prescribing, classification of medication errors, and how to achieve quality in health care prescribing worldwide and in Saudi Arabia.