A better understanding of the challenges in the diagnosis of progressive supranuclear palsy (PSP), the most common atypical parkinsonian neurodegenerative disorder, has led to improving its diagnostic accuracy. Similarly, a better understanding of the role of tau mutations, mitochondrial complex I inhibitors, oxidative injury, and inflammation in neurodegeneration has led to an unraveling of potential risk factors for the development of PSP. These advances are explained in detail in this review.