Many of our organs, such as the lungs, kidneys, or the vascular system, consist of networks of branched epithelial tubes, which perform vital functions, such as gas exchange, nutrient transport, and excretion. In case of the vascular system and the kidneys, initially separate units of epithelial tubes fuse to form interconnected tubular networks. Aberrant connections of blood vessels can cause vascular pathologies, such as arteriovenous malformations. Despite their medical significance, the cellular and molecular mechanisms that govern epithelial tube fusion are not well understood. The process of tube fusion involves directed migration of cells towards the fusion point, formation of a new cell-cell junction, and finally the connection of adjacent tubes, either through connecting pre-existing lumina or through de-novo lumen formation at the fusion joint. We aim to understand the mechanism of membrane fusion during the connection of tracheal tubes. We use in vivo cell labeling techniques combined with high-resolution light and electron microscopy to define the intermediates of the fusion process at the cellular and ultrastructural level. To identify new components of the underlying cellular machinery, we characterize fusion-defective mutations, which we have isolated in genetic screens performed in the lab. Answering basic questions about lumen formation and conversion of cellular topology in the Drosophila tracheal tube fusion model will provide a conceptual framework for elucidating similar processes, such as vascular anastomosis and pronephric duct fusion, in more complex vertebrate systems.