The recent approval of two safe and effective treatments for patients with idiopathic pulmonary fibrosis (IPF) had as a direct consequence the absolute need for an accurate and early diagnosis. The standard approach to IPF diagnosis has proven to be effective and emphasized the importance of clinical and laboratory evaluations to exclude known causes of pulmonary fibrosis. At the same time, chest high-resolution computed tomography (HRCT) has proven to be the crucial initial diagnostic test, by identifying those patients who should undergo surgical lung biopsy to secure a confident diagnosis and an adequate treatment. However, this diagnostic approach showed over the years some limitations. First, many suspected IPF patients present with atypical HRCT appearances and at the same time are unfit (or unwilling) for surgical lung biopsy, therefore making a confident diagnosis of IPF impossible. Although the current recommendations indicate the need for an iterative multidisciplinary process incorporating available clinical, laboratory, imaging and histological features, recent work has identified new tools which might improve the overall accuracy of this process. Genomic techniques have been already applied to molecularly phenotype patients with interstitial lung disease and it is likely that in the near future clinicians will utilize blood or lung-specific molecular markers in combination with other clinical, physiological, or imaging features. The availability of new sampling procedures (e.g. transbronchial cryobiopsies), together with innovative imaging technologies (e.g. microCT) will most likely support and enhance diagnostic efforts, refine prognostic recommendations and ultimately influence therapeutic options.