Larger proteins (above molecular weight 50 kDa) usually show slow motional tumbling in solution, which facilitates the decay of NMR signal, resulting in poor signal-to-noise. In the past twenty years, researchers have tried to overcome this problem with higher molecular weight by improvement of hardware (higher magnetic field and cryoprobe), optimization of pulse sequences for lager molecules, and development of isotope-labeling techniques. Actually, GroEL/ES complex (${approx}$ 900 kDa) was successfully studied using combination of above techniques. Among the techniques used in large molecular studies, the impact of isotope-labeling for large molecules study is summarized and discussed here.