Learning Objectives: On successful completion of this activity, participants should be able to (1) provide an introduction to machine learning, neural networks, and deep learning; (2) discuss common machine learning algorithms with illustrative examples and figures; and (3) compare machine learning algorithms and provide guidance on selection for a given application. Financial Disclosure: Sandra E. Black received in-kind funding to her institution from GE Healthcare and Avid Pharmaceuticals. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through April 2022. This article, the first in a 2-part series, provides an introduction to machine learning (ML) in a nuclear medicine context. This part addresses the history of ML and describes common algorithms, with illustrations of when they can be helpful in nuclear medicine. Part 2 focuses on current contributions of ML to our field, addresses future expectations and limitations, and provides a critical appraisal of what ML can and cannot do.