Timeout expired. The timeout period elapsed prior to completion of the operation or the server is not responding. The statement has been terminated

I have many users on my web site (20000-60000 per day), which is a download site for mobile files. I have remote access to my server (windows server 2008-R2).
I’ve received “Server is unavailable” errors before, but am now seeing a connection timeout error.

I’m not familiar with this – why does it occur and how can I fix it?