Background: Pharmaceutical costs are the fastest-growing healthcare expense in most countries, meaning that physicians are required to adopt cost-conscious behavior in their medication prescribing practice. This study aimed to assess the levels of cost-consciousness and the familiarity with cost concepts among physicians working in Saudi Arabia. Methods: This was a cross-sectional, questionnaire-based study conducted in the period from May to October 2019. It included physicians employed in Saudi Arabia in different workplaces and settings. Results: A total of 239 physicians responded to the survey, about 85% of whom had never received any formal education or training in health economics or pharmacoeconomics. Almost all of them (94%) agreed that physicians need to take a more prominent role in limiting the use of unnecessary medications and three-quarters (75.3%) of them agreed that trying to contain medications cost is the responsibility of every physician. The factors that were found to affect cost-consciousness behavior were gender, as well as knowledge of and familiarity with cost-effectiveness as one of the economic evaluation concepts. Higher cost-consciousness was observed among those who were knowledgeable about the terms cost-containment (p=0.039) and cost-effectiveness (p=0.002) and who were familiar with the concept of cost-effectiveness (p<0.001). Conclusion: The physicians agreed that costs should be borne in mind when prescribing medicines. However, it also appears that physicians are not overly confident about their knowledge of healthcare costs. Factors such as medical ethics and patient demand and satisfaction were perceived as the most common barriers for considering cost in physicians’ therapeutic decision-making in their daily practice.