Silica or silicon dioxides (SiO₂) are naturally occurring substances that comprise the vast majority of the earth's crust. Because of their prevalence and commercial applications, they have been widely studied for their potential to induce pulmonary fibrosis and other disorders. Historically, the focus in the workplace has been on the development of inflammation and fibrotic lung disease, the basis for promulgating workplace standards to protect workers. Crystalline silica (CS) polymorphs, predominantly quartz and cristobalite, are used in industry but are different in their mineralogy, chemistry, surface features, size dimensions and association with other elements naturally and during industrial applications. Epidemiologic, clinical and experimental studies in the literature historically have predominantly focused on quartz polymorphs. Thus, in this review, we summarize past scientific evaluations and recent peer-reviewed literature with an emphasis on cristobalite, in an attempt to determine whether quartz and cristobalite polymorphs differ in their health effects, toxicity and other properties that may dictate the need for various standards of protection in the workplace. In addition to current epidemiological and clinical reports, we review in vivo studies in rodents as well as cell culture studies that shed light on mechanisms intrinsic to the toxicity, altered cell responses and protective or defense mechanisms in response to these minerals. The medical and scientific literature indicates that the mechanisms of injury and potential causation of inflammation and fibrotic lung disease are similar for quartz and cristobalite. Our analysis of these data suggests similar occupational exposure limits (OELs) for these minerals in the workplace.