<p>Lettuce is one of the most important and economical vegetable crops in the world. Many cultivar varieties of lettuce are commercially available and known as morphotypes; some of the common ones include romaine lettuce, leafy, headed crispy, and oil-yielding. There is a wide range of pathogens, including bacteria, fungi, viruses and oomycetes, which cause severe crop yield-reducing diseases in lettuce. The review describes the various pathogens causing serious diseases in lettuce, resulting in huge economic and market losses. The molecular mechanisms underlying pathogenesis are scant, and the management practices need to be strengthened to address the associated crop losses and to increase productivity. This article provides a holistic approach to the pathogenesis of lettuce.</p> Graphical abstract <p></p>