Cancer is an exceedingly complex disease that is orchestrated and driven by a combination of multiple aberrantly regulated processes. The nature and depth of involvement of individual events vary between cancer types, and in lung cancer, the deregulation of the epigenetic machinery, the tumor microenvironment and the immune system appear to be especially relevant. The contribution of microRNAs to carcinogenesis and cancer progression is well established with many reports and investigations describing the involvement of microRNAs in lung cancer, however most of these studies have concentrated on single microRNA-target relations and have not adequately addressed the complexity of their interactions. In this review, we focus, in part, on the role of microRNAs in the epigenetic regulation of lung cancer where they act as active molecules modulating enzymes that take part in methylation-mediated silencing and chromatin remodeling. Additionally, we highlight their contribution in controlling and modulating the tumor microenvironment and finally, we describe their role in the critical alteration of essential molecules that influence the immune system in lung cancer development and progression.