Actinomycetes are rich source of polycyclic aromatic molecules, known as polyketides, which include many clinically important antibiotics and anticancer drugs. These polyketides, exemplified by anthracyclines, angucyclines and tetracyclines, are a large group of natural products with diverse structures and biological activities. They are synthesized by the so-called type-2 polyketide synthases (PKSs). Type 2 PKS gene clusters consist of the so-called minimal PKS (consisting of ketosynthase heterodimer (KSα and KSβ) and an acyl carrier protein (ACP)) and keto-reductases, cyclases, aromatases and late tailoring enzymes designated as post-PKS enzymes. In recent years, numerous genome sequencing projects revealed the diversity and complexity of biosynthetic polyketide gene clusters. Bioinformatic approaches are needed in order to study geene cluster encoding type-2 PKS, and thus taylor-made bioinformatic approaches are needed to identify, annotate and predict the chemical output from their biosynthetic gene clusters. Gene cloning and expression technologies are being developed to allow the expression of silent biosynthetic gene clusters. Therefore, in the scope of this work we have carried review on potential approaches to study and identify novel type-2 PKS gene clusters.