Smoking induced lung diseases were extremely rare prior to the twentieth century. With commercialization and introduction of machine-made cigarettes, worldwide use skyrocketed and several new pulmonary diseases have been recognized. The majority of pulmonary diseases caused by cigarette smoke (CS) are inflammatory in origin. Airway epithelial cells and alveolar macrophages have altered inflammatory signaling in response to CS, which leads to recruitment of lymphocytes, eosinophils, neutrophils, and mast cells to the lungs - depending on the signaling pathway (NFκB, AMPK, JNK, p38 and STAT3) activated. Multiple proteins are up-regulated and secreted in response to CS exposure, and many of these have immunomodulatory activities which contribute to disease pathogenesis. In particular, metalloproteases (MMP)-9 and -12, surfactant (SP-D), antimicrobial peptides (LL-37 and human beta defensin 2), and interleukins (IL)-1, -6, -8 and -17 have been found in higher quantities in the lungs of smokers with ongoing inflammation. However, many underlying mechanisms of smoking induced inflammatory diseases are not yet known. We review here the known cellular and molecular mechanisms of CS induced diseases, including chronic obstructive pulmonary disease (COPD), respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), acute eosinophilic pneumonia, chronic rhinosinusitis, pulmonary Langerhans' cell histiocytosis, and chronic bacterial infections. We also discuss inflammation induced by second-hand and third-hand smoke exposure, and the pulmonary diseases that result. New targeted anti-inflammatory therapeutic options are currently under investigation, and hopefully will yield promising results for the treatment of these highly prevalent smoking induced diseases.