Here we describe our attempts to study the interaction of nanomodified surfaces with neurons and macrophages. Surfaces with nano-sized topographies produced by UV lithography, electrochemical etching, nanoimprint lithography, microdispensing, or by electrospinning of plastic nanofibers or by making plastic replicas of the extracellular matrix with nanoresolution were found to guide neurite outgrowth extending from the dorsal root and the superior cervical ganglion in tissue culture. Ordered arrays of nanowires acted as particularly potent guides for the neurites. Loose nanowires activated the macrophages. We conclude that relatively simple nanomodifications of surfaces can be utilized to guide neurites. This property could potentially be applied to guide neurite outgrowth on implants in the nervous system intended for recordings of electrical and/or chemical activities.