<p>The evolution of simulation techniques in biomolecules and biomaterials has led to a plethora of simulation times that are increasingly achieving timescales observed in biological events. This review addresses the challenges of conventional molecular dynamics simulations in such systems and explains how enhanced sampling techniques (like umbrella sampling, accelerated molecular dynamics, replica exchange molecular dynamics, metadynamics, Markov state models, milestoning) coupled with upgraded computing resources, can accelerate sampling of configurational space in various biomolecular systems like peptides, proteins, nucleic acids, and lipid membranes. A comparative analysis of such techniques with respect to timescales is also carried out for diverse biomaterial interfaces (such as biomolecular conjugates with graphene, carbon nanotubes, biopolymers and fullerenes) where it is seen that such advanced techniques can yield additional insights into free energies, binding affinities, orientations and interactions. A futuristic glimpse into recent techniques employing supercomputing, optimised workflows, and deep learning approaches for high throughput simulations is also presented in this review. It is expected that the evolution of multi-scale and hybrid approaches can pave the way towards exploring the balance of technique and timescale in biological system simulations in a synergistic manner.</p> Graphical abstract <p>The interplay between diverse simulation techniques and timescales in deciding the course of biological simulations involving proteins, nucleic acids, membranes as well as biomaterial interfaces has been reviewed in this work. Challenges and future prospects of enhanced sampling approaches are balanced in this amalgamate of simulation stories.</p>