Many decisions in General Medicine have to be made in the paucity of well-researched information. Despite the existence of evidence-based guidelines, physicians may perceive obstacles in implementing these in clinical practice. Intolerance to uncertainty may result in a tendency to perceive ambiguous situations as sources of threat. Variability in treatment, choice of medical specialty, increased personal anxiety, increased test ordering tendencies, decrease comfort with geriatric and psychological problems have been correlated with intolerance to uncertainty. Various Instruments and scales are currently available to measure physician's uncertainty. Quantitative and qualitative techniques of managing uncertainty include shared decision-making, meticulous history-taking and evaluation, exclusion of worrisome diagnosis, ability to critically appraise current literature and establishing trust with patient.