Machine learning (ML) models for analyzing medical data are critical for both accelerating development of novel diagnostic and treatment strategies and improving the accuracy of medical care delivery. Our objective was to comprehensively review supervised ML models for diagnosis or treatment prediction. Publications indexed in PubMed were reviewed to identify articles utilizing supervised predictive ML models in medicine. Articles published between 01/01/2020–01/01/2022 were included in this review. Initially, PubMed was searched using MeSH major terms, and if more extensive search results were needed, a broader search was applied (titles/abstracts).PubMed indexed 21,268 published articles (MeSH Major topic) describing ML methods implemented in medicine. Of those, 11,726 articles were published within the last 2 years. Most of the published ML models in medicine in the last two years were different types of deep learning models (about 75%). Fifty articles were included in this review.Almost all categories of disease were subjects of ML predictions. Positive and negative factors in each of the scenarios need to be evaluated before the most optimal ML model is selected. Domain knowledge and collaborations between physicians and ML experts can improve the selection and prediction performance of ML models in medicine and facilitate implementation in clinical practice. Predictive ML models could provide recommendations to recruit suitable patients for clinical trials. Prediction ML models may contribute to development of more effective diagnostic and therapeutic choices, founded on evidence-based medicine. A broad range of methodological approaches have been taken toward this goal, and those approaches are presented here with their various advantages and disadvantages.AUTHOR SUMMARYOver the last decade, there has been rapid development of Machine learning (ML) methods to analyze Big Data in medicine. ML is aimed to make the computer learn from past experiences and make predictions by recognizing patterns in medical data. We performed a comprehensive systematic literature review of recent publications (last two years), indexed in PubMed/MEDLINE that have described either traditional or deep supervised prediction ML models in medicine. We identified 21,268 articles describing ML implementation in medicine. 11,726 articles were published in the last 2 years. We presented the number of publications describing each of the most often ML methods to show current trends in development of these models. Most of the recently published ML models in medicine were deep learning models. We found that the understanding of disease is likely to lead to more accurate prediction. An important dilemma is the selection of optimal ML models for a specific task, considering amount and type of available data. Domain knowledge and collaborations between physicians and ML experts can improve the prediction performance of ML models, which could help clinicians to select the most effective diagnostic and therapeutic choices available and decrease medical errors.