The potential of algorithm-based clinical decision support (CDS) in healthcare continues to increase with the growing field of artificial intelligence (AI)-enabled CDS. The use of these technologies to support clinicians, patients, and health systems is still quite new, and to date, implementors and regulators are still identifying the best processes and practices to ensure the effective, safe, and equitable use of these technology solutions. To assist individuals and organizations interested in implementation of algorithm-based CDS and AI-enabled CDS in healthcare, this article reviews the important regulatory decisions that form the landscape within which algorithm-based CDS has emerged, modern governance frameworks used to oversee these CDS systems, nuances in evaluation and monitoring throughout the CDS life cycle, best practices for real-world implementation, safety and equity considerations, and avenues for future collaboration and innovation.