我在这里找不到一个简单的解决方案，所以我希望有人会喜欢这个:

更新2018-09-20

把这段代码放在Program.cs中:

using System.Diagnostics;

static void Main()
{
    Process thisProcess = Process.GetCurrentProcess();
    Process[] allProcesses = Process.GetProcessesByName(thisProcess.ProcessName);
    if (allProcesses.Length > 1)
    {
        // Don't put a MessageBox in here because the user could spam this MessageBox.
        return;
    }

    // Optional code. If you don't want that someone runs your ".exe" with a different name:

    string exeName = AppDomain.CurrentDomain.FriendlyName;
    // in debug mode, don't forget that you don't use your normal .exe name.
    // Debug uses the .vshost.exe.
    if (exeName != "the name of your executable.exe") 
    {
        // You can add a MessageBox here if you want.
        // To point out to users that the name got changed and maybe what the name should be or something like that^^ 
        MessageBox.Show("The executable name should be \"the name of your executable.exe\"", 
            "Wrong executable name", MessageBoxButtons.OK, MessageBoxIcon.Error);
        return;
    }

    // Following code is default code:
    Application.EnableVisualStyles();
    Application.SetCompatibleTextRenderingDefault(false);
    Application.Run(new MainForm());
}

使用互斥量解决方案:

using System;
using System.Windows.Forms;
using System.Threading;

namespace OneAndOnlyOne
{
static class Program
{
    static String _mutexID = " // generate guid"
    /// <summary>
    /// The main entry point for the application.
    /// </summary>
    [STAThread]
    static void Main()
    {
        Application.EnableVisualStyles();
        Application.SetCompatibleTextRenderingDefault(false);

        Boolean _isNotRunning;
        using (Mutex _mutex = new Mutex(true, _mutexID, out _isNotRunning))
        {
            if (_isNotRunning)
            {
                Application.Run(new Form1());
            }
            else
            {
                MessageBox.Show("An instance is already running.");
                return;
            }
        }
    }
}
}

基于Matt Davis的答案，为方便起见包装成一个类。

public static class SingleAppInstanceChecker
{
    /// <summary>
    /// Arbitrary unique string
    /// </summary>
    private static Mutex _mutex = new Mutex(true, "0d12ad74-026f-40c3-bdae-e178ddee8602");

    public static bool IsNotRunning()
    {
        return _mutex.WaitOne(TimeSpan.Zero, true);
    }
}

使用示例:

private void Application_Startup(object sender, StartupEventArgs e)
{
    if (!SingleAppInstanceChecker.IsNotRunning())
    {
        MessageBox.Show("Application is already running.");

        // Exit application using:
        // Environment.Exit(1);
        // Application.Current.Shutdown();
        // Etc...

        return;
    }
    
    // Allow startup and continue with normal processing
    // ...
}

永远不要使用命名互斥来实现单实例应用程序(至少在生产代码中不要这样做)。恶意代码可以很容易地DoS(拒绝服务)你的屁股…

这里有一个解决方案:

Protected Overrides Sub OnStartup(e As StartupEventArgs)
    Const appName As String = "TestApp"
    Dim createdNew As Boolean
    _mutex = New Mutex(True, appName, createdNew)
    If Not createdNew Then
        'app is already running! Exiting the application
        MessageBox.Show("Application is already running.")
        Application.Current.Shutdown()
    End If
    MyBase.OnStartup(e)
End Sub

请检查这里提出的解决方案，它使用信号量来确定现有实例是否已经在运行，适用于WPF应用程序，并且可以通过使用TcpListener和TcpClient将参数从第二个实例传递给第一个已经运行的实例:

它不仅适用于。net Framework，也适用于。net Core。