The rapidly changing environment of healthcare is shifting towards value-based care and engaging patients as active participants in their wellness. This shift presents a unique opportunity to transform the role of laboratory diagnostic services to actively collaborate with providers, health systems, and patients to improve outcomes and reduce overall costs. The national focus addressing chronic disease provides a striking opportunity for the Clinical Lab 2.0 (CL2.0) movement to transform our scientific approach from reactive confirmation to proactive prediction. The use of longitudinal laboratory data has the potential to support early detection, predict risk of disease, and positively impact population health. This manuscript conveys how the CL2.0 Lab-Initiated Care Models and evidence collected through the Multi-Institutional Demonstration Projects conducted through the Project Santa Fe Foundation (PSFF) help demonstrate the critical value of laboratory services in the ever-evolving healthcare landscape.