Inherited platelet disorders (IPDs) are rare genetic conditions that impair platelet production or function, leading to bleeding of varying severity and, in some patients, development of multisystemic disorders. This chapter provides a summary of IPD caused by defects in platelet signal transduction pathways, which are essential for platelet activation, adhesion and aggregation. Molecular abnormalities in genes encoding key proteins for the activation of the integrin αIIbβ3, such as the guanine nucleotide exchange factors RasGRP2, the small GTPase Rap1 and the adaptor proteins Kindlin-3, result in diseases including platelet-type bleeding disorder-18 (BDPLT18), syndromic thrombocytopenia with developmental abnormalities and leukocyte adhesion deficiency type III (LAD-III), respectively. Defects in thromboxane A2 (TXA2) synthesis enzymes, including cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1) and thromboxane synthase (TBXAS-1), also impair platelet aggregation. Additionally, mutations in phospholipase C isoforms (PLCβ and PLCγ) disrupt platelet calcium signalling. G-protein alterations, particularly in Gαq and Gαi subunits, impair G-protein coupled receptor (GPCR)-mediated platelet activation. Gain-of-function mutations in regulators of G-proteins, such as RGS18, cause excessive inhibition of platelet signalling. Furthermore, miscellaneous defects in proteins, including Src family kinases and cytoskeletal regulators, also contribute to platelet dysfunction and favour bleeding. The advent of high-throughput genetic sequencing has enhanced the identification of these molecular abnormalities, thereby facilitating precise diagnoses of IPD. It is imperative to comprehend these mechanisms in order to develop targeted therapies and enhance clinical outcomes for patients suffering from IPD.