It is now recognized that asthma incorporates a broad spectrum of syndromes with varying clinical manifestations. Future improvements in asthma treatment will require a clear characterization of these asthma phenotypes and the cellular mechanisms underlying these clinical manifestations. Herein, we will describe the current knowledge of asthma biology. This will include a review of the early pioneers in asthma and allergy, how this work led to our understanding of TH1 and TH2 cytokines, and the development of the "hygiene hypothesis." We will discuss the utility and limitations of the TH1-TH2 model of asthma in animal and human studies, and how this knowledge addresses controversies surrounding the hygiene hypothesis and other competing models. We will discuss novel therapies that have been developed based on mechanistic understanding of asthma pathobiology, including successes and shortcomings of these therapies. We will review the early work that led to the recognition of "asthma phenotypes." This will include the early discovery of various inflammatory subtypes in asthma and how these inflammatory subtypes correlate with response to therapy. Finally, we will describe recent discoveries in asthma biology that will include the role of the airway epithelium in asthma pathogenesis, novel cytokines important in asthma that may serve as novel therapeutic targets, and the identification of newly described innate immune cells and their role in asthma. Improved understanding of the complex biology underpinning the various asthma phenotypes is critical for our ability to optimize treatment for all patients that suffer from asthma and critical asthma syndromes.