Introduction: Myofibroblasts are the primary executor and influencer in lung fibrosis. Latest studies on lung myofibroblast pathobiology have significantly advanced the understanding of the pathogenesis of lung fibrosis and shed new light on strategies targeting these cells to treat this disease. Areas covered: This article reviewed the most recent progresses, mainly within the last 5 years, on the definition, origin, activity regulation, and targeting of lung myofibroblasts in lung fibrosis. We did a literature search on PubMed using the keywords below from the dates 2010 to 2020. Expert opinion: With the improved cell lineage characterization and the advent of scRNA-seq, the field is having much better picture of the lung myofibroblast origin and mesenchymal heterogeneity. Additionally, cellular metabolism has emerged as a key regulation of lung myofibroblast pathogenic phenotype and is a promising therapeutic target for treating a variety of lung fibrotic disorders.