Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder characterized by changes in behaviour and language dysfunction. Two broad pathological subdivisions of FTLD are recognized in a recent classification scheme based on biochemical features: tau-positive pathology due to the accumulation of various forms of the microtubule-associated protein tau, such as FTLD with Pick bodies and corticobasal degeneration; and tau-negative pathology such as frontotemporal lobar degeneration with ubiquitin/TDP-43-immunoreactive inclusions. Etiologically based treatments aim to target the mechanisms underlying the accumulation of these abnormal proteins in these conditions. It is essential for us to develop biomarkers that support the accurate diagnosis of the specific diseases causing FTLD. These biomarkers also can be useful in assessing efficacy during treatment trials. This review summarizes the epidemiologic, clinical, neuropsychological, imaging and cerebrospinal fluid (CSF) biomarker features that can help identify these pathologically defined conditions during life.