This special issue of Multiscale Modeling and Simulation: A SIAM Interdisciplinary Journal, on multiscale modeling in biology, stems from the workshop "Biocomplexity V: Multiscale Modeling in Biology," held August 14--17, 2003, at the University of Notre Dame and organized jointly by the Interdisciplinary Center for the Study of Biocomplexity at the University of Notre Dame, the Biocomplexity Institute at Indiana University, and Los Alamos National Laboratory, in cooperation with the Society for Industrial and Applied Mathematics. The workshop took place in conjunction with the Notre Dame Conference on Partial Differential Equations with Applications. Modeling and simulation are becoming central research tools in biology. The most advanced of these efforts have focused on single levels or scales, e.g., genomic/proteomic, cellular, tissue, organ, whole body, behavioral, and population. We now need to develop the software tools and mathematical approaches to integrate models from micro-scales to macro-scales in a seamless fashion. Such multiscale models are essential if we are to produce quantitative, predictive models of complex biological behaviors such as embryonic development, cancer, cytoskeletal function, and ecosystems. At the same time, developing the abstractions to integrate between scales will lead to a much deeper understanding of the universal or generic features of biological phenomena. This special issue of MMS presents a state-of-the-art view of the multiscale approach to modeling in biology. The papers in this collection combine theoretical and computational approaches to model a variety of important multiscale biological phenomena in areas ranging from immunology to pattern formation to cytoskeletal dynamics and calcium wave propagation. As the papers in this issue illustrate, researchers in this interdisciplinary field have developed a rich variety of techniques and applied them to a variety of biological problems at multiple scales. In certain applications, such as the study of intracellular calcium cycles (Tsaneva-Atanasova, Shuttleworth, Yule, Thompson, and Sneyd), subcellular results have explained behaviors at larger scales, e.g., experimentally observed cell and tissue behaviors. Excitable medium and pattern formation methodologies apply to a wide spectrum of tissue behaviors (ten Tusscher and Panfilov). Continuum models for excitable media have the attraction of being amenable to both analytical and numerical methods. Population models (Doering, Sargsyan, and Sander) that describe ecosystem scales in terms of agents and smaller-scale variables are similarly rich and immediately apply to the study of epidemics and their control through drugs. The paper by Murray and Perelson also includes genetic behaviors to study the population-leveleffects of various drugs and mutations on HIV. Clearly, addressing multiple biological scales requires a heterogeneous model framework; Gammack, Ganguli, Marino, Segovia-Juarez, and Kirschner integrate discrete and continuum models to explore the immune response to tuberculosis. Biological cells provide an obvious integration level between subcellular and molecular scales on the one hand, and tissues and organs on the other. Jonsson and Levchenko explain the behaviors of yeast colonies using a model for single cells that considers the cell-level phenomena of growth and division. Chemical signals usually mediate cell responses; Erban and Othmer discuss the role this microscale plays in the resulting macroscopic behavior of embryonic spatial pattern formation. Banks and Pinter present a probabilistic model for hysteresis and shear waves at the tissue scale and its possible medical applications, another case requiring heterogeneous models and approaches to treat multiple biological scales. The hybrid models typical of systems biology tend to mix continuous, discrete, deterministic, and probabilistic approaches to address important questions in morphogenesis and regeneration. Recent advances in developing a three-dimensional hybrid framework for modeling morphogenesis, the pattern of structural development of an organism or its organs, promise a truly integrated approach to multiscale biological processes. Morphogenesis involves differentiation, growth, death, and migration of cells as well as changes in the shapes of cells and tissues and the secretion and absorption of extracellular materials. Rubinstein, Jacobson, and Mogilner provide a good example of this philosophy in their multiscale model of lamellopodia; their composite model ranges from the molecular scale of actin machinery to the micron-scale lamellopodium itself, to illustrate the many model extensions and modifications that moving from one-dimensional to three-dimensional models requires. Alarcon, Byrne, and Maini take a similar approach to tumor growth. One key area for future research is the integration of genomic and macroscopic approaches to produce more complete models which include both genetic and generic phenomena. We would like to express our special thanks to Dr. James M. Hyman, for the idea of a conference volume and help in every step of creating this special issue. We also want to thank Dr. Leah Edelstein-Keshet for her advice and help in preparing this issue.