<p>Photosynthetic organisms lie at the heart of the food chain, with plants acting as the primary carbon source in terrestrial ecosystems, essential for sustaining both human and animal life. The outbreaks of diseases in plants caused by fungi, bacteria, viruses, or protozoa have a considerable impact on the economy and global food supply. Therefore, the use of safe alternatives to control them is highly desirable. According to one of the main models currently accepted for plant–pathogen interaction, resistance responses to attacks by disease-causing microorganisms involve signalling pathways, signal transduction, regulation of gene expression, and production of proteins and small molecules. These molecules, known as secondary metabolites (natural products), play significant role in the various defence mechanisms as components of plant chemical defence against biotic and abiotic stress. Due to advances in genetics and molecular biology research, numerous biosynthetic pathways to phytoalexins, phytohormones, antimicrobial and signalling compounds have been elucidated, as well as their regulation. The activation of these plant metabolic pathways may lead to an incompatible response, preventing the occurrence, or the establishment of the disease, with metabolic synthesis and exchange between the involved organisms. Understanding the interaction between plants and pathogens, as well as plant defence mechanisms, is crucial for developing new approaches to minimize the damage caused by pathogen attacks on agricultural crops worldwide. This review comprehensively addresses plant–pathogen interaction by delving into the molecular recognition and immune responses in plants and exploring the intricate signalling pathways mediated by phytohormones and other secondary metabolites.</p>