Non-small cell lung carcinomas (NSCLC) account for about 80% of lung cancers and their remarkable heterogeneity manifests in histology, pathogenesis, prognosis, and response to treatments. Recent advances in molecular characterization help stratifying NSCLC patients for their potential benefit from targeting therapies. However, the fundamental mechanisms underlying the tumoral heterogeneity remain poorly understood. Expression profiling of many microRNAs (miRNAs) in various normal and disease tissues demonstrated unique spatial and temporal expression patterns and some miRNAs have been functionally characterized as oncogenes or tumor suppressor genes. Genome-wide screening identified specific miRNA expression signatures associated with clinical outcome of NSCLC patients. A group of miRNAs that has enriched expression in normal lung was found down regulated in NSCLC and may function as tumor suppressor genes. In this review we: a) summarize the current understanding of the critical role that miRNAs play in normal cell functions and in disease biology especially in lung cancer tumorigenesis, b) highlight their potential as biomarkers for lung cancer risk stratification, outcome prediction and classification of histologic subtypes, c) critically assess current knowledge on lung-enriched miRNAs and expression of their predicted target genes in NSCLC and d) evaluate their potential as circulating biomarkers and therapeutic targets in lung cancer.