The National Center for Biotechnology Information Entrez Direct (EDirect) software facilitates programmatic access to numerous biomedical, chemical, and literature databases from within a Unix terminal. EDirect has traditionally been used for command line access to NCBI data within the fields of computational biology and bioinformatics. This article describes how EDirect can be used for programmatic retrieval of small molecule and related chemical information from the PubChem and PubMed databases, useful for the chemical and cheminformatics communities. Several use cases are presented that demonstrate using EDirect in applications such as retrieving small molecule chemical property information, compound bibliometric data, and literature references. In addition, more advanced use cases are discussed that demonstrate how to incorporate EDirect searches into reproducible data analysis workflows, for example, with data visualization programs and cheminformatics toolkits. Since EDirect is a collection of command line programs, the syntax to perform programmatic search queries and related operations is simplified and suitable for beginners. This is in contrast to common approaches of programmatic chemical information searching using computational notebooks that may require additional training and computer programming skills. As a result of the more beginner friendly learning curve, EDirect may be particularly useful for chemical information professionals that often teach one time workshops where there is limited time to introduce programming concepts to students. This article concludes with an example implementation of teaching EDirect and a review of the limitations. Approximately 20 EDirect scripts useful for programmatic small molecule chemical information searching are included in this Article and in the Supporting Information. All EDirect scripts shared have a permissible open source license, and educators are highly encouraged to adapt the scripts and workflows as desired.