Background: Clinical guidelines have been the key resource for clinicians around the world to guide clinical care. The ways in which these guidelines are written and promoted to clinicians predict their uptake in day-to-day practice. We sought to evaluate the factors that determine good clinical guidelines and their uptake among medical practitioners. Results: Key predictors of guideline uptake include clinician intrinsic factors such as awareness, familiarity, disagreement, and inertia of practice. Extrinsic factors pertaining to the patient and health system also predict guideline uptake. While significant benefits have been shown in the literature by virtue of guidelines, there are minimal disadvantages. Conclusion: There are many factors involved in predicting the use of clinical guidelines in practice. It is essential to identify these and continue to support their use, as appropriately designed clinical practice guidelines can provide immense benefits to all those involved in the health system.